Robin B. Kanarek

The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight

Food intake and body weight are determined by a complex interaction of regulatory pathways. To elucidate the contribution of the endogenous peptide cholecystokinin, mice lacking functional cholecystokinin-A receptors were generated by targeted gene disruption. To explore the role of the cholecystokinin-A receptor in mediating satiety, food intake of cholecystokinin-A receptor-/- mice was compared with the corresponding intakes of wild-type animals and mice lacking the other known cholecystokinin receptor subtype, cholecystokinin-B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease food intake in mice lacking cholecystokinin-A receptors. In contrast, cholecystokinin diminished food intake by up to 90% in wild-type and cholecystokinin-B/gastrin receptor-/- mice. Together, these findings indicate that cholecystokinin-induced inhibition of food intake is mediated by the cholecystokinin-A receptor. To explore the long-term consequences of either cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a function of age was compared between freely fed wild-type and mutant animals. Both cholecystokinin-A and cholecystokinin-B/gastrin receptor-/- mice maintained normal body weight well into adult life. In addition, each of the two receptor-/- strains had normal pancreatic morphology and were normoglycemic. Our results suggest that although cholecystokinin plays a role in the short-term inhibition of food intake, this pathway is not essential for the long-term maintenance of body weight.

Effect of breakfast composition on cognitive processes in elementary school children.

The relationship between breakfast composition and cognitive performance was examined in elementary school children. Two experiments compared the effects of two common U.S. breakfast foods and no breakfast on childrens cognition. Using a within-participant design, once a week for 3 weeks, children consumed one of two breakfasts or no breakfast and then completed a battery of cognitive tests. The two breakfasts were instant oatmeal and ready-to-eat cereal, which were similar in energy, but differed in macronutrient composition, processing characteristics, effects on digestion and metabolism, and glycemic score. Results with 9 to 11 year-olds replicated previous findings showing that breakfast intake enhances cognitive performance, particularly on tasks requiring processing of a complex visual display. The results extend previous findings by showing differential effects of breakfast type. Boys and girls showed enhanced spatial memory and girls showed improved short-term memory after consuming oatmeal. Results with 6 to 8 year-olds also showed effects of breakfast type. Younger children had better spatial memory and better auditory attention and girls exhibited better short-term memory after consuming oatmeal. Due to compositional differences in protein and fiber content, glycemic scores, and rate of digestion, oatmeal may provide a slower and more sustained energy source and consequently result in cognitive enhancement compared to low-fiber high glycemic ready-to-eat cereal. These results have important practical implications, suggesting the importance of what children consume for breakfast before school.

Hormonal milieu affects tailflick latency in female rats and may be attenuated by access to sucrose

The steroid hormones estrogen (E) and progesterone (P) are known to modify pain sensitivity; however, the relative role of each of these hormones in this process is not well understood. To systematically investigate the effects of E and P on nociception, pain sensitivity was assessed under several hormone conditions. Tailflick (TF) latencies were measured every other day in 10 cycling female rats and 10 female rats during luteal functioning (pseudopregnancy). Thirty ovariectomized (OVX) rats were tested for TF latency following administration of 10 micrograms estradiol benzoate (EB) and either 0.0, 0.5, or 1.0 mg of P. Significant differences in TF latency were seen across days of the estrous cycle but not during luteal functioning. Tailflick latencies during luteal functioning were elevated relative to latencies in normally cycling animals. Among OVX rats, those administered EB and P (1.0 mg) displayed significant reductions in TF latency compared to vehicle controls. As a separate line of research indicated that consumption of highly palatable foods modified pain sensitivity, whether chronic sucrose consumption might overide the influence of hormones on nociception was examined. Ovariectomized rats given EB and P (0.0, 0.5, or 1.0 mg) were allowed chronic exposure to a 32% sucrose solution. Our preliminary findings suggest that chronic sucrose consumption attenuates hormonally induced differences in nociception.

Diet and estrous cycle influence pain sensitivity in rats

Effects of estrous cycle and acute and chronic access to palatable fluids on tail-flick latency and opiate-induced analgesia were assessed in 124 female Long Evans rats. Following three consistent cycles, rats were water deprived for 8 h and then given ad lib access to 20 ml of either water, a 32% sucrose solution, or corn oil for 5 h. Nociceptive testing was conducted immediately preceding and 30, 60, and 90 min following an SC injection of morphine sulfate (7.5 mg/kg). Diestrus rats had prolonged premorphine tail-flick latencies compared to rats in proestrus. Rats that consumed corn oil had longer tail-flick latencies preceding and 30 min following morphine injections than rats that drank water or the sucrose solution. Rats were retested after they had ad lib access to the same fluid for 3 weeks. No estrous cycle differences were noted following chronic consumption. Rats with chronic access to sucrose showed increased baseline pain sensitivity and increased morphine-induced analgesia at 30, 60, and 90 min postinjection. These data support the notion that palatable fluid consumption attenuates estrous cycle-dependent differences in pain sensitivity.

Morphine selectively influences macronutrient intake in the rat

Dietary self-selection of the three macronutrients, protein, carbohydrate and fat, was examined in male rats following the administration of three doses of morphine sulphate: 10 mg, 15 mg, and 30 mg/kg body weight. Intakes of all three macronutrients were suppressed in a dose-dependent manner for a two-hour period following morphine administration. Both protein and carbohydrate intakes remained suppressed for a six-hour feeding period after morphine injections. In contrast, animals increased fat intake during the final four hours of the six-hour feeding period resulting in an overall increase in fat intake.

Modifications of nutrient selection induced by naloxone in rats.

Total caloric intake and dietary self-selection of the three macronutrients protein, fat, and carbohydrate were examined in male rats maintained on a 6-h feeding schedule following the administration of the opioid antagonist naloxone HCl (0.1, 1.0, and 10.0 mg/kg IP). Total caloric intake (calculated as the sum of caloric intakes from each of the macronutrients) was decreased for up to 2 h following naloxone administration. By the end of the 6-h feeding period, however, no differences in total caloric intakes were observed as a function of naloxone injections. Examination of intakes of the individual macronutrients revealed that naloxone differentially affected fat, carbohydrate, and protein consumption. Across the 6-h feeding period, animals consumed less calories from the fat ration following all three doses of naloxone than after saline injections. Carbohydrate intake was decreased for up to 2 h following naloxone injections, but returned to control values by the end of the 6-h feeding period. Protein intake, in contrast to fat and carbohydrate intakes, did not vary as a function of naloxone administration. Results of the present experiment are contrasted with patterns of dietary self-selection observed following morphine administration.

Developmental aspects of sucrose-induced obesity in rats.

Daily caloric intakes and body weights were measured from weaning to 70 days of age in male Sprague-Dawley rats given access to either a standard laboratory diet and water, or the standard diet, a 32% sucrose solution and water. Lee index of obesity (3 square root body weight/naso-anal length) and fasting blood glucose levels were determined at 46, 57, and 70 days of age. Animals were sacrificed at 70 days, and body composition analyses were performed. Aniamls given access to the sucrose solution consumed significantly more calories per day than animals given only the standard diet. Sucrose animals took approximately 50 to 60% of their daily caloric intake from the sugar solution. Despite the greater caloric intakes of the sucrose animals, sucrose and control animals did not differ in body weight. While there were no differences in body weights between the two groups, the Lee Index of obesity was significantly greater in the sucrose animals than in controls as early as 46 days of age. Fasting blood glucose levels were significantly lower in sucrose animals than in controls at both 46 and 57 days of age. Direct determinations of body compositions when animals were 70 days of age revealed that animals with access to sucrose had significantly greater percentages of body fat and lower percentages of body protein than controls.

Diet-induced obesity and spatial cognition in young male rats

Abstract Recent work suggests that obesity may adversely affect cognitive behavior. To examine this suggestion, the effects of feeding a standard chow diet, and either supplemental sugar or fat on the development of obesity and performance on a test of spatial learning, the Morris Water Maze (MWM), were assessed in young male Long–Evans rats. Rats given access to a sucrose solution or dietary fat in addition to the chow diet consumed approximately 10% more calories per day, gained more weight, and had larger epididymal fat pads than rats fed the chow diet alone. Moreover, rats fed the supplemental sucrose took significantly more time to find a hidden platform in the MWM than rats fed the chow diet alone or chow and supplemental fat. Additionally, when tested 10 days after the initial training trials, rats given sucrose displayed deficits in long-term spatial memory. After 6 weeks on the diets, fasting blood glucose and serum triglyceride concentrations were significantly higher in sucrose-fed rats than in rats eating only the standard diet. These results indicate that diet-induced obesity resulting from excess sucrose intake, but not fat intake, in young animals impairs spatial learning and memory. It is hypothesized that these deficits arise from metabolic insults that leave the brain vulnerable to alterations in insulin sensitivity and glucose metabolism.

2-Deoxy-D-glucose induced feeding: relation to diet palatability.

Abstract Adult male rats fed either ground Purina Laboratory Chow or the same diet adulterated with 0.5% quinine hydrochloride were tested for feeding in response to the administration of 2-deoxy-D-glucose (2-DG). Three doses of 2-DG were used, 250, 500, and 750 mg/kg of body weight. During a six-hr test period, rats given ground Purina Laboratory Chow ate significantly more following intraperitoneal (IP) injections of 250 and 500 mg/kg of 2-DG than following IP injections of physiological saline. Food intake of animals given Purina Chow also increased after administration of 750 mg/kg of 2-DG, but intake was not significantly different from that following saline injections. In contrast to rats maintained on the unadulterated diet, rats given quinine-adulterated chow did not increase intake over saline values during the six-hr test period following administration of 250 and 500 mg/kg of 2-DG, and actually decreased intake after injection of 750 mg/kg of 2-DG. Results are discussed with respect to the role of diet palatability in determining food intake in hungry animals.

Differential effects of amphetamine and fenfluramine on dietary self-selection in rats ☆

Daily caloric intakes and dietary self-selection of the three macronutrients, protein, fat and carbohydrate were examined in female rats following administration of d-amphetamine sulfate (0.0, 0.5, 1.0 and 2.0 mg/kg, IP) or fenfluramine hydrochloride (0.0, 1.5, 3.0 and 6.0 mg/kg, IP). Animals were maintained on ground Purina Chow or one of two self-selection regimes, one with a high-caloric fat ration (7.85 kcal/g) and the other with a fat ration isocaloric to the carbohydrate and protein rations (3.76 kcal/g). Animals received drug injections at the beginning of a daily 8-hour feeding period with nutrient intakes measured at 2, 4 and 8 hrs following injections. While both amphetamine and fenfluramine lef to dose-related decreases in total caloric intakes, the two drugs resulted in different temporal patterns of feeding. Amphetamine produced its greatest effect on caloric intake during the first 2 hours of the feeding period, whereas fenfluramine suppressed caloric intake equivalently across the 8-hour feeding period. The two anorectic drugs also led to different patterns of nutrient choice. When animals were given the high-caloric fat ration, amphetamine selectively decreased fat intake while fenfluramine produced decreases in both protein and fat intakes, sparing carbohydrate intake. In contrast, when animals were given the isocaloric fat ration, amphetamine resulted in a general suppression of nutrient intakes while fenfluramine led to a sustained decrease in fat intake with a relative sparing of protein and carbohydrate consumption.